The present invention relates to novel deoxy-1.4;3.6-dianhydrohexitols and nitric acid esters thereof having a vasodilative activity.
Organic nitrates, for example, nitroglycerine, have been clinically used for angina pectoris in sublingual administration, and it has not orally been administered. Hence, nitroglycerine was useless for preventive therapy for attacks of angina pectoris and the administration of nitroglycerine was limited to emergency care on attacks of angina pectoris.
On the other hand, it has been known that hexitol derivatives, e.g., isosorbide dinitrate are useful in preventing or relieving accute anginal attacks [The Merck Index. 10th edition, page 751 (1983)]. Nevertheless, therapeutic effects of isosorbide dinitrate for angina pectoris or coronary deficiency were not enough in view of the pharmacological activities and side effects such as headache, vomiting, etc. On industrial viewpoint, both organic nitrate and isosorbide dinitrate should be prepared and handled under strict regulation for prevention of disasters.
As an improved hexitol derivative, 5-(4-methylpiperazino)-5-deoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate having a vasodilative activity was developed and disclosed in Japanese Published Unexamined Patent Application No. 58686/82 [U.S. Pat. No. 4,363,805 and EP-A No. 44940].
However, novel hexitol derivatives are desired for improvement in pharmacological activities and water solubility, as a medicine for angina pectoris.